BGB-58067 in Newly Diagnosed Glioblastoma Patients With MTAP-Deleted Tumors

NCT07485049 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2025-24
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-center, Phase 0/2 trial designed to enroll up to 78 total participants with suspected newly diagnosed glioblastoma (nGBM) who are scheduled for surgical resection to accrue at least 14 participants in Arm A and 10 participants in Arm B. The trial will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of BGB-58067. The study is composed of a Phase 0 and expansion Phase 2 component. The Phase 0 primary endpoint will be suppression of symmetric dimethylarginine (SDMA) in tumor tissue measured by immunohistochemistry (IHC). The Phase 2 primary endpoint will be 12-month overall survival rate (OS12). The Phase 0 secondary endpoint will be to characterize the PK of BGB-58067 in tumor tissue, plasma, and cerebrospinal fluid (CSF). The Phase 2 secondary endpoints will include assessing the safety profile of BGB-58067 and evaluating clinical efficacy of BGB 58067 using overall survival (OS) and the 6-month progression-free survival rate (PFS6) estimated by Kaplan-Meier (K-M) methods.

Conditions

Glioblastoma (GBM)

Keywords

MTAP-Deleted; MGMT Methylation; Methylthioadenosine Phosphorylase; O6-Methylguanine-DNA Methyltransferase; PRMT5 Inhibitor; PRMT5i; Newly Diagnosed Glioblastoma; Newly Diagnosed Grade 4 Glioma

Outcome Measures

Primary Outcomes (2)

• Phase 0: Proportion of Participants with ≥ 50% Decrease from Baseline in SDMA Expression, or with SDMA H-Score ≤ 70, in Phase 0 Tumor Tissue Collected Intraoperatively

  Decrease in SDMA expression in tumor tissue collected during Phase 0 surgery relative to baseline will be used if pre-treatment biopsy tissue is available. Otherwise, H-score ≤ 70 in tumor tissue collected during Phase 0 surgery will be used.

  Intraoperatively

• Phase 2: Proportion of Participants Alive at 12 Months

  Overall survival at 12 months (OS12)

  Date of Phase 0 surgery to date of death due to any cause, assessed up to 12 months

Secondary Outcomes (14)

• Phase 0: Mean Total Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

  Intraoperatively

• Phase 0: Mean Unbound Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

  Intraoperatively

• Phase 0: Median Total Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

  Intraoperatively

• Phase 0: Median Unbound Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

  Intraoperatively

• Phase 0: Mean CSF Concentration of BGB-58067

  Intraoperatively

Study Arms (2)

Arm A: Unmethylated-MGMT GBM-BGB-58067 Monotherapy

EXPERIMENTAL

Participants with unmethylated-MGMT and MTAP-deleted GBM demonstrating a positive PD response after Phase 0 surgery.

Drug: BGB-58067

Arm B: Methylated-MGMT GBM-BGB-58067 + TMZ Concurrent Therapy

EXPERIMENTAL

Participants with methylated-MGMT and MTAP-deleted GBM demonstrating a positive PD response after Phase 0 surgery.

Drug: BGB-58067

Interventions

BGB-58067 DRUG

During Phase 0, a high dose of BGB-58067 will be administered over several days prior to surgery to determine PK and PD effect in resected tumor tissue. During Phase 2, BGB-58067 dosing will continue with standard radiation therapy (RT) followed with adjuvant therapy. Participants will receive monotherapy or concurrent therapy with temozolomide (TMZ) based on MGMT methylation status.

Arm A: Unmethylated-MGMT GBM-BGB-58067 Monotherapy; Arm B: Methylated-MGMT GBM-BGB-58067 + TMZ Concurrent Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Suspected newly diagnosed glioblastoma according to 2021 WHO criteria who have not received any tumor directed intervention other than biopsy.
• \. Has measurable disease (preoperatively), defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.
• \. Age ≥ 18 at time of consent.
• \. Has a performance status of ≤ 2 on the ECOG scale.
• \. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
• Adequate Bone Marrow Function Absolute neutrophil count ≥ 1500/μL (≥ 1.5 x 109/L) Platelets (at time of surgery) ≥ 100,000/μL (≥ 100 x 109/L) Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without pRBC transfusion within prior 2 weeks.)
• Adequate Hepatic Function Total Bilirubin ≤ 1.5x ULN (Participants with Gilbert's syndrome with a total bilirubin ≤ 3x ULN and direct bilirubin ≤ 1.5x ULN will be permitted.) AST (SGOT) ≤ 2.5x institutional ULN (Participants with liver metastases with ALT \< 5x ULN will be permitted) ALT (SGPT) ≤ 2.5x institutional ULN (Participants with liver metastases with ALT \< 5x ULN will be permitted.)
• Adequate Renal Function eGFR ≥ 60 mL/min/1.73 m2 (Calculated as individualized eGFR using the CKD-EPI formula \[2021\]) If measured or calculated GFR (e.g., creatinine clearance; mGFR) is required or used: ≥ 60 mL/min
• Adequate Metabolic Function Albumin ≥ 2.8 g/dL
• Adequate Coagulation INR or PT and aPTT ≤ 1.5x ULN
• \. For females of childbearing potential:
• Must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment (within 24 hours of first dose of study treatment); in rare cases where hCG is suspected to be elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out possible pregnancy.
• Must use a highly effective method of contraception (with a failure rate of \<1% per year and low user dependency) for at least 28 days prior to treatment, and agree to use such a method during study participation and for an additional 6 months after final study drug administration.
• Agrees not to breastfeed starting at screening, during study participation, and for 6 months after final study drug administration.
• Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction starting at screening, during study participation, and for 6 months after final study drug administration.

You may not qualify if:

• \. Unable to undergo MRI of the brain with intravenous (IV) contrast.
• \. Has a known active systemic bacterial infection (on IV antibiotics or has fever \> 38.5°C at time of initiating study treatment) or fungal infection, or has a detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[e.g., hepatitis B surface antigen positive\]). NOTE: Screening of viral infection is not required for enrollment.
• \. Has cardiovascular abnormalities including:
• LVEF \< 50%
• History of prolonged QTc, or QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation \> 480 msec, except for right bundle branch block.
• Uncontrolled/symptomatic or significant cardiovascular conditions within 6 months prior to enrollment, including but not limited to any of the following: cardiac angioplasty or stenting, unstable angina pectoris, myocardial infarction, stroke/transient ischemic attack, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, New York Heart Association (NYHA) class III or IV congestive heart failure, pericarditis, atrial fibrillation or other arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
• \. Has symptomatic or radiographic leptomeningeal disease.
• \. Has other known concurrent severe psychiatric and/or uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol.
• \. Has received prior treatment with another investigational drug or other intervention within 5 half lives of the investigational product, whichever is longer.
• \. Has received prior treatment with another PRMT5 inhibitor.
• \. Has known allergic reactions to components of BGB-58067.
• \. Patients who require ongoing treatment with a strong CYP3A or CYP2C8 inhibitor or inducer, ≤ 5 half-lives or ≤ 14 days, whichever is shorter or known. Consider using alternative medications, per Investigator judgment.
• \. Has received a live/attenuated vaccine within 30 days of anticipated first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted.
• \. Is pregnant or breastfeeding.

Sponsors & Collaborators

• Nader Sanai: lead
• BeOne Medicines: collaborator

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Nader Sanai, MD

  Ivy Brain Tumor Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phase 0 Navigator

CONTACT

602-406-8605; research@ivybraintumorcenter.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Ivy Brain Tumor Center

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 20, 2026
• Study Start: May 7, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)